Acute Modulation of Stereotyped High Frequency Oscillations with a Closed-Loop Brain Interchange System in Drug Resistant Epilepsy

项目总结： 高频振荡(HFO)的颅内脑电(IEEG)有可能识别手术切除 耐药癫痫患者的面积/发作起始区(SOZ)然而，多份报告表明， HFO不仅可由癫痫脑组织产生，也可由非癫痫部位产生，通常包括 能言善辩的区域，如运动、视觉和语言皮质。在这个项目中，我们提出了初步证据 反复出现的波形模式，可能足以区分病理性HFO和生理性HFO。 具体地说，我们表明SOZ重复地生成具有类似 波形形态，而从SOZ外记录的事件是不规则的。这种形态 Pattern是一种强有力的神经生物标志物，可以将SOZ与多个患者的其他脑区隔离 始终如一。虽然这些有希望的初步结果已经到位，但刻板印象的功能效用 HFO在闭环癫痫控制系统中的作用尚不清楚。 到目前为止，还不太清楚SOZ产生的刻板印象的HFO是否可以通过 植入式系统。如果能够实现这一点，那么HFO可以战略性地作为一种神经生物标记物转化为 闭环式癫痫控制应用。我们假设病理性刻板印象的HFO可以被捕获 利用Cortec的植入性脑交换(BIC)系统和这些事件的空间地形图 由植入式系统利用来提供有针对性的电刺激，以实现癫痫控制。使用 在癫痫监测单元(EMU)内的急性设置，该项目将研究捕获 使用新的BIC系统对HFO事件进行定型，并将检测结果与使用 市面上可以买到的功放。如果我们研究的第一阶段(AIM-1)取得成功，在晚些时候 第二阶段(AIM-2)，同样是在动车组中，我们将向这些大脑部位提供有针对性的电刺激 与使用BIC的刻板印象的HFO有关。我们将研究这种闭环系统的调制效应 通过监测特征事件的变化来实施刺激策略，例如尖峰、癫痫放电、涟漪 以及快速的涟漪。 如果成功，这个闭环系统不必等待癫痫发作开始就可以传递刺激 一开始就是由NeuroPace的RNS系统完成的。相比之下，该系统将监测空间地形 并向这些区域提供有针对性的刺激，以防止癫痫的发生。 如果我们在急性环境下的研究结果成功，我们将进行临床试验并运行我们的 方法在慢性非卧床环境中植入BIC系统。 1

Project Summary: High frequency oscillations (HFOs) of intracranial EEG (iEEG) have the potential to identify the surgical resection area/seizure onset zone (SOZ) in patients with drug resistant epilepsy. However, multiple reports indicate that HFOs can be generated not only by epileptic cerebral tissue but also by non-epileptic sites often including eloquent regions such as motor, visual and language cortices. In this project, we present the initial evidence of a recurrent waveform pattern that may be sufficient to distinguish pathological HFOs from physiological ones. Specifically, we show that the SOZ repeatedly generates sets of stereotypical HFOs with similar waveform morphology whereas the events recorded from out of SOZ were irregular. This morphological pattern served as a robust neurobiomarker to isolate SOZ from other brain areas in multiple patients consistently. While these promising preliminary results are in place, the functional utility of stereotyped HFOs in a closed-loop seizure control system remains unknown. As of today, not much is known whether the stereotyped HFOs generated by the SOZ can be detected with an implantable system. If this can be achieved, then HFOs can be strategically translated as a neurobiomarker into closed-loop seizure control applications. We hypothesize that pathologic stereotyped HFOs can be captured with the implantable Brain Interchange (BIC) system of CorTec and spatial topography of these events can be utilized by the implantable system to deliver targeted electrical stimulation to achieve seizure control. Using an acute setup within the epilepsy monitoring unit (EMU), this project will investigate the feasibility of capturing stereotyped HFO events using the new BIC system and compare the detection results to those obtained with the commercially available amplifier. If the first phase (Aim-1) of our study becomes successful, later in the second phase (Aim-2), once again in the EMU, we will deliver targeted electrical stimulation to those brain sites associated with stereotyped HFOs using the BIC. We will investigate the modulatory effects of this closed-loop stimulation strategy by monitoring the changes in signature events such as spikes, epileptic discharges, ripples and fast ripples. If successful, this closed-loop system does not have to wait for a seizure to start in order to deliver the stimulation at its onset as done by the RNS system of Neuropace. In contrast, the system will monitor the spatial topography and rate of stereotyped HFOs and deliver targeted stimulation to these areas to prevent seizures from occurring. If the outcomes of our research in acute setting become successful, we will execute a clinical trial and run our methods with the implanted BIC system in a chronic ambulatory setting. 1